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1.
Ig Sanita Pubbl ; 80(3): 111-123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36453204

RESUMO

BACKGROUND: Italy is one of the main destinations for winter tourism. Specifically, the country can currently count on more than 5.700 km of ski runs, served by more than 1.700 lift facilities Objective. The purpose of this study has been the analysis of injuries in ski resorts in a continuous period spanning over several seasons (17 years). In addition, the possible effect of safety law enforcements, introduced in the selected period, were considered. MATERIAL AND METHODS: A ski injuries database, prepared as a duty of policemen involved in rescue activity and consisting of 246616 records of injuries for the period from 7th December 2002 to 31st December 2019, has been analysed for qualitative and quantitative variables. RESULTS: The majority of injuries (58%) occurred on slopes with medium difficulties. After the introduction of national ski safety law (Law 363/2003), a strong diffusion of protective helmet has been noticed. The adoption of the helmet has significantly reduced cranio-facial injuries both in children and in adults. Moreover, no death events were recorded in the database after the introduction of Law 363/2003. The diffusion of ski accident insurance programs is slowly increasing, even if in the year 2019 approximately 38% of skiers still didn't have an insurance program. DISCUSSION AND CONCLUSIONS: It is possible to speculate that the introduction of a national ski safety law had a positive effect on injuries reduction. At the same time, collected data underlined several critical points that seem, at least in part, addressed by the law revision performed in 2021.


Assuntos
Coleta de Dados , Adulto , Criança , Humanos , Itália/epidemiologia , Estações do Ano
2.
Artigo em Inglês | MEDLINE | ID: mdl-30402124

RESUMO

Electrochemical reduced water (ERW) has been proposed to have beneficial effects on human health due to its rich content of H2 and the presence of platinum nanoparticles with antioxidant effects. Many studies have demonstrated that ERW scavenging properties are able to reduce the damage caused by oxidative stress in different experimental models. Although few in vivo studies have been reported, it has been demonstrated that ERW may display anticancer effects by induction of tumor cells apoptosis and reduction of both angiogenesis and inflammation. In this study, we show that ERW treatment of MCF-7, MDA-MB-453, and mouse (TUBO) breast cancer cells inhibited cell survival in a time-dependent fashion. ERW decreased ErbB2/neu expression and impaired pERK1/ERK2 and AKT phosphorylation in breast cancer cells. In addition, ERW treatment induced apoptosis of breast cancer cell lines independently of the status of p53 and ER and PR receptors. Our in vivo results showed that ERW treatment of transgenic BALB-neuT mice delayed the development of mammary tumors compared to the control. In addition, ERW induced a significant prolongation of tumor-free survival and a reduction in tumor multiplicity. Overall, these results suggest a potential beneficial role of ERW in inhibiting cancer cells growth.

3.
Leg Med (Tokyo) ; 35: 34-43, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268689

RESUMO

The analysis of microorganism population is crucial in several medical fields. This is especially true in legal and occupational medicine, where the specialist can be asked to perform an evaluation of several environmental matrices. In these two medical fields an accurate microbiological analysis is part of a wide process aimed to the definition of the interactions between human beings and environment. In legal medicine it is important to deserve attention to the identification of microbiological traces in order to better understand past events, while in occupational and preventive medicine the microbiological evaluation of environmental samples is crucial for an effective risk management and the definition of safety procedures. The achievement of these objectives requires the comprehension of microbial biodiversity and not only the identification of few biomarkers. In the present paper, the complexity of this process is highlighted through the presentation of typical scenarios where microorganism population analyses are relevant in legal medicine and occupational medicine. The similarities between the microbiological approach in legal and occupational medicine lead to the sharing of laboratory approaches. A description of technological evolution shows how new protocols and procedures are supporting a wider microbiological comprehension of specimens. The development of molecular tools has opened new opportunities, but it has underlined the need for the implementation of new standardized procedures dedicated to these medical fields, where science and medicine interact with the law. In addition, the rapid evolution of massive parallel sequencing technologies requires the implementation of new bioinformatic tools with a user-friendly interface.


Assuntos
Microbiologia Ambiental , Medicina Legal , Medicina do Trabalho , Humanos
4.
J Forensic Sci ; 62(1): 192-196, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27907225

RESUMO

The identification of vaginal fluids in forensic examinations plays an important role in crime scene reconstruction. Molecular detection of vaginal bacterial communities can lead to the correct discrimination of body fluids. These kinds of studies can be performed through multiplex real-time PCR using primers for a specific selection of bacteria. The availability of next-generation sequencing (NGS) protocols provided for the extension of the analysis to evaluate the prokaryotes present in specimens. In this study, DNA was extracted from 18 samples (vaginal, oral, fecal, yoghurt) and analyzed by real-time PCR and NGS. The comparison between the two approaches has demonstrated that the information developed through NGS can augment the more conventional real-time PCR detection of a few key bacterial species to provide a more probative result and the correct identification of vaginal fluid from samples that are more forensically challenged.


Assuntos
Muco do Colo Uterino/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Vagina/microbiologia , DNA Bacteriano/genética , Fezes/microbiologia , Feminino , Genética Forense , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Saliva/microbiologia
5.
Genome Announc ; 4(5)2016 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-27609919

RESUMO

The slightly thermophilic bacterium Tepidimonas taiwanensis strain VT154-175 has been isolated from a hot spring in the area of Viterbo, Italy. The whole draft genome of 2.9 Mb obtained by paired-end next-generation sequencing and divided into 60 scaffolds is presented.

6.
Work ; 52(2): 385-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26409361

RESUMO

BACKGROUND: In Italy, students from Movement Science (MS) Degree Courses often work in sport and recreational facilities before graduation. OBJECTIVE: The employment conditions of Movement Science students working in sport/recreational facilities were investigated, and the management and structural features of the facilities were evaluated, including safety policies. Regional differences were also considered. METHODS: Questionnaires were administered to undergraduate and graduate students (N = 4,217) in 17 Universities. Students' perceptions of the quality of the facilities where they had been employed was evaluated using multivariate analysis. A latent class model with covariates was used to evaluate how variables relating to participants, employment facilities or regions influence their opinions. RESULTS: A high proportion of MS students were employed in sporting facilities (undergraduate level: 33% ; graduate level: 55%), in most cases without any formal employment contracts. Both the structural and hygienic features, as well as the professional knowledge of the staff, were considered good to excellent by the majority of participants (about 70%). Communication of the basic behavioral rules was considered adequate by 61-63% of undergraduate students and 71-75% of graduate students, while nearly half of the participants were dissatisfied with the staff safety training. Correlations between the perceived good structural/hygienic conditions, the presence of regulations and training programs for the staff were investigated. Differences regarding occupational level and safety training among different regions of Italy were also observed. CONCLUSIONS: Italian students in Movement Science were easily employed in sport/recreational facilities, but frequently without a formal contract. This is a consequence of the lack of specific regulations in the field of recreational/leisure employment and could have negative implications, especially in terms of safety.


Assuntos
Emprego/estatística & dados numéricos , Saúde Ocupacional , Instalações Esportivas e Recreacionais/organização & administração , Estudantes de Ciências da Saúde/estatística & dados numéricos , Adolescente , Adulto , Educação de Pós-Graduação , Emprego/legislação & jurisprudência , Feminino , Humanos , Capacitação em Serviço , Itália , Cinesiologia Aplicada , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional/educação , Papel (figurativo) , Esportes , Instalações Esportivas e Recreacionais/legislação & jurisprudência , Inquéritos e Questionários , Adulto Jovem
7.
J Prosthet Dent ; 114(4): 602-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25979449

RESUMO

STATEMENT OF PROBLEM: Metal ions released into the oral cavity from dental prosthesis alloys may damage the cellular metabolism or proliferation and cause hypersensitivity or allergies. The oral cavity environment is particularly prone to corrosion due to saliva, microorganisms, and pH variations. PURPOSE: The purpose of this in vitro study was to evaluate the ion release of chromium, cobalt, and iron from the Co-Cr alloys used for traditionally cast and computer-aided design/computer-aided manufacturing dental devices after interaction with oral bacteria and different pH conditions. MATERIAL AND METHODS: All specimens were prepared from currently available alloys, polished, and immersed in 3 different pH media (artificial saliva [pH 2.3] and 6.5% and 0.9% saline solution [pH 7.1]). Specimens were also incubated in the presence of the bacterium Eikenella corrodens. Solutions were analyzed with an atomic absorption spectrometer after 15 and 30 days in the chemical corrosion test and 30 days in the biocorrosion test to detect ions released in different solutions. An ANOVA test was used to evaluate statistically significant differences among the percentages of metal corrosion ion release values. RESULTS: The greatest amount of element release was seen after 30 days: 4.964 ppm of casting alloy, 2.642 ppm of milling alloy, and 2.351 ppm of laser metal sintering. CONCLUSIONS: With the exception of casting alloy under acidic conditions, no significant differences were found, even after exposure to bacteria.


Assuntos
Ligas de Cromo/química , Cromo/análise , Cobalto/análise , Ligas Dentárias/química , Cromo/química , Cobalto/química , Desenho Assistido por Computador , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Saliva Artificial
8.
J Water Health ; 12(3): 564-72, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25252360

RESUMO

Natural swimming ponds (NSPs) are a new type of recreational water facility characterized by the substitution of traditional disinfection with biodepuration. While this feature meets esthetic desires of users, specific concerns on public health issues have been raised by the scientific community and local authorities. The absence of a European directive applicable to these environments leaves each country without specific and harmonized indications. The present work describes the local/national policy situation, describing adopted parameters and monitoring activities. All documents underline the need for appropriate microbiological analysis and correct water management.


Assuntos
Política de Saúde/legislação & jurisprudência , Lagoas/microbiologia , Saúde Pública/legislação & jurisprudência , Recreação , Piscinas/legislação & jurisprudência , Europa (Continente) , Piscinas/classificação
10.
Bull Environ Contam Toxicol ; 92(1): 75-80, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24217626

RESUMO

We monitored heavy metal (As, Cd, Hg, and Pb) concentrations in surface water, sediments, and oligochaetes in four major rivers in Calabria (southern Italy) over the course of 1 year. As, Cd, and Pb showed accumulation factors of 10(3)-10(5) for water to sediment and 1-10 for sediment to oligochaetes. Hg showed a water to sediment accumulation factor of 10-100. Finally, Hg concentrations exceeded the Italian quality standard for freshwater in all of the rivers, and As concentrations in sediments exceeded the respective Canadian standard. However, the application of an ecological risk assessment method indicated low risks for all monitored rivers.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Rios/química , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Itália , Medição de Risco , Poluição Química da Água/estatística & dados numéricos
11.
J Forensic Leg Med ; 21: 60-3, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24365693

RESUMO

Identification of vaginal fluids is an important step in the process of sexual assaults confirmation. Advances in both microbiology and molecular biology defined technical approaches allowing the discrimination of body fluids. These protocols are based on the identification of specific bacterial communities by microfloraDNA (mfDNA) amplification. A multiplex real time-PCR assay (ForFLUID kit) has been developed for identifying biological fluids and for discrimination among vaginal, oral and fecal samples. In order to test its efficacy and reliability of the assay in the identification of vaginal fluids, an interlaboratory evaluation has been performed on homogeneous vaginal swabs. All the involved laboratories were able to correctly recognize all the vaginal swabs, and no false positives were identified when the assay was applied on non-vaginal samples. The assay represents an useful molecular tool that can be easily adopted by forensic geneticists involved in vaginal fluid identification.


Assuntos
Muco do Colo Uterino/microbiologia , DNA Bacteriano/genética , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Vagina/microbiologia , Adulto , Enterococcus faecalis/genética , Enterococcus faecalis/isolamento & purificação , Feminino , Medicina Legal/normas , Humanos , Laboratórios/normas , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Staphylococcus/genética , Staphylococcus/isolamento & purificação , Streptococcus/genética , Streptococcus/isolamento & purificação
12.
Ig Sanita Pubbl ; 68(4): 613-24, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23086151

RESUMO

A working group of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI) has translated into Italian the World Health Organization (WHO) guidance document "Water safety in buildings" published in 2011. The document is intended to provide guidance on implementing the WHO Guidelines for drinking-water quality. In the present article, the authors describe the framework of the WHO document and summarize the main points discussed.


Assuntos
Segurança , Água , Itália , Guias de Prática Clínica como Assunto , Traduções , Organização Mundial da Saúde
13.
Recenti Prog Med ; 103(4): 164-72, 2012 Apr.
Artigo em Italiano | MEDLINE | ID: mdl-22561996

RESUMO

An active lifestyle represents a significant factor in prevention of osteoporosis. Evidences on multifactorial etiology allowed to develop a plan for risk evaluation and for an integrated screening approach. Adapted physical activity plays a relevant role in secondary prevention, also when performed in swimming pools.


Assuntos
Exercício Físico , Osteoporose/prevenção & controle , Prevenção Secundária/métodos , Humanos , Atividade Motora
14.
Forensic Sci Int Genet ; 6(5): 559-64, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22364791

RESUMO

The discrimination of body fluids in forensic examinations can play an important role in crime scene reconstruction. Conventional methods rely on the detection of antigens or enzymatic activity, limiting detection sensitivity and specificity, particularly on old forensic samples. Methods based on human RNA analysis are not easily applicable to samples exposed to harsh and degrading environments. An alternative approach based on the identification of prokaryotic genomes was developed. Specific bacterial communities are characteristic typical of different human non-sterile body fluids: the molecular characterization of a microbial signature, and not the typing of single bacterial species, can effectively lead to univocal identification of these fluids. A multiplex real time PCR assay was developed using oligonucleotide mixtures targeting genomes specific for a selected group of bacteria. Microflora DNA (mfDNA) was extracted from vaginal, oral and fecal clinical swabs. In addition forensic samples were processed. Vaginal samples showed a strong specific signal for bacteria of the female genital tract. Oral samples clearly showed signal for bacteria present in saliva, and in fecal samples the main signal was from Enterococcaceae. Vaginal casework samples showed results comparable to freshly collected ones; moreover the DNA extracted was successfully used for STR typing. Also mixtures of body fluids were analyzed, providing a microbiological signature compatible with the presence of microbes of oral, fecal and vaginal origin. The presented method can be useful in identifying biological fluids, and it is based on DNA technologies already available in forensic laboratories and feasible for further high throughput automation.


Assuntos
Líquidos Corporais/metabolismo , DNA Bacteriano/genética , Vagina/metabolismo , Sequência de Bases , Primers do DNA , Feminino , Humanos , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase em Tempo Real , Vagina/microbiologia
15.
Ig Sanita Pubbl ; 68(6): 863-73, 2012.
Artigo em Italiano | MEDLINE | ID: mdl-23369998

RESUMO

The use of thermal waters in swimming pools for recreational use is widespread in Europe and in the rest of the world. The biological and chemical properties of spa waters make it difficult to treat them with conventional disinfection methods. The authors present an overview of European and international laws and regulations on this subject and highlight their strengths and gaps.


Assuntos
Balneologia/normas , Recreação , Humanos , Internacionalidade
16.
Cancer Res ; 70(6): 2476-84, 2010 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-20197467

RESUMO

ERBB2/neu and Notch signaling are known to be deregulated in many human cancers. However, pathway cross-talk and dependencies are not well understood. In this study, we use an ERBB2-transgenic mouse model of breast cancer (neuT) to show that Notch signaling plays a critical role in tumor maintenance. Inhibition of the Notch pathway with a gamma-secretase inhibitor (GSI) decreased both the Notch and the mammalian target of rapamycin/AKT pathways. Antitumor activity resulting from GSI treatment was associated with decreased cell proliferation as measured by Ki67 and decreased expression of glucose transporter Glut1. Positron emission tomography (PET) imaging showed that the functional consequences of decreased Glut1 translated to reduced glucose uptake and correlated with antitumor effects as measured by micro-computed tomography imaging. The decrease of Glut1 in neuT tumors was also observed in several human breast cancer cell lines following GSI treatment. We provide evidence that approximately 27% of ERBB2-positive human breast cancer specimens display high expression of HES1, phospho-S6RP, and GLUT1. Together, these results suggest that pathways downstream of Notch signaling are, at least in part, responsible for promoting tumor growth in neuT and also active in both neuT and a subset of human breast cancers. These findings suggest that GSI may provide therapeutic benefit to a subset of ERBB2-positive breast cancers and that [(18)F]FDG-PET imaging may be useful in monitoring clinical response.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Glucose/farmacocinética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína Oncogênica v-akt/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptor ErbB-2/metabolismo , Receptores Notch/metabolismo , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Óxidos S-Cíclicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Fluordesoxiglucose F18/farmacocinética , Transportador de Glucose Tipo 1/biossíntese , Humanos , Neoplasias Mamárias Experimentais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Proteína Oncogênica v-akt/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR , Tiadiazóis/farmacologia
17.
Mol Ther ; 17(10): 1804-13, 2009 10.
Artigo em Inglês | MEDLINE | ID: mdl-19623161

RESUMO

The human telomerase reverse transcriptase (hTERT) is an attractive target for human cancer vaccination because its expression is reactivated in most human tumors. We have evaluated the ability of DNA electroporation (DNA-EP) and adenovirus serotype 6 (Ad6) to induce immune responses against hTERT in nonhuman primates (NHPs) (Macaca mulatta). Vaccination was effective in all treated animals, and the adaptive immune response remained detectable and long lasting without side effects. To further enhance the efficacy of the hTERT vaccine, we evaluated the combination of hTERT vaccine and a novel TLR9 agonist, referred to as immunomodulatory oligonucleotide (IMO). Monkeys were dosed weekly with IMO concurrently with the vaccine regimen and showed increases in cytokine secretion and activation of natural killer (NK) cells compared with the group that received vaccine alone. Using a peptide array, a specific profile of B-cell reactive epitopes was identified when hTERT vaccine was combined with IMO. The combination of IMO with hTERT genetic vaccine did not impact vaccine-induced TERT-specific cell-mediated immunity. Our results show that appropriate combination of a DNA-EP/Ad6-based cancer vaccine against hTERT with IMO induces multiple effects on innate and adaptive immune responses in NHPs.


Assuntos
Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Telomerase/imunologia , Receptor Toll-Like 9/agonistas , Adenoviridae/genética , Animais , Eletroporação , Epitopos de Linfócito B/imunologia , Imunidade Celular/imunologia , Imunidade Inata/genética , Interferon-alfa/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Macaca mulatta , Telomerase/genética
18.
Clin Cancer Res ; 15(5): 1575-84, 2009 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-19240169

RESUMO

PURPOSE: Oligodeoxynucleotides containing unmethylated CpG dinucleotides induce innate and adaptive immunity through Toll-like receptor 9 (TLR9). In the present study, we have examined the ability of a novel agonist of TLR9, called immunomodulatory oligonucleotide (IMO), to enhance effects of a HER-2/neu plasmid DNA electroporation/adenovirus (DNA-EP/Ad) vaccine. EXPERIMENTAL DESIGN: BALB/NeuT mice were treated with DNA-EP vaccine alone, IMO alone, or the combination of two agents starting at week 13, when all mice showed mammary neoplasia. Tumor growth and survival were documented. Antibody and CD8+ T-cell responses were determined. Peptide microarray analysis of sera was carried out to identify immunoreactive epitopes. Additionally, microCT and microPET imaging was carried out in an advanced-stage tumor model starting treatment at week 17 in BALB/NeuT mice. RESULTS: The combination of DNA-EP and IMO resulted in significant tumor regression or delay to tumor progression. 2-Deoxy-2-[18F]fluoro-D-glucose microPET and microCT imaging of mice showed reduced tumor size in the DNA-EP/IMO combination treatment group. Mice treated with the combination produced greater antibody titers with IgG2a isotype switch and antibody-dependent cellular cytotoxicity activity than did mice treated with DNA-EP vaccine. An immunogenic B-cell linear epitope, r70, within the HER-2 dimerization domain was identified through microarray analysis. Heterologous DNA-EP/Ad vaccination combined with IMO increased mice survival. CONCLUSION: The combination of HER-2/neu genetic vaccine and novel agonist of TLR9 had potent antitumor activity associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities. These results support possible clinical trials of the combination of DNA-EP/Ad-based cancer vaccines and IMO.


Assuntos
Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/terapia , Plasmídeos/administração & dosagem , Receptor ErbB-2/imunologia , Receptor Toll-Like 9/fisiologia , Vacinas de DNA/uso terapêutico , Adenoviridae/genética , Fosfatase Alcalina/metabolismo , Animais , Citotoxicidade Celular Dependente de Anticorpos , Células Apresentadoras de Antígenos/imunologia , Terapia Combinada , DNA/administração & dosagem , Dimerização , Eletroporação , Ensaio de Imunoadsorção Enzimática , Feminino , Interleucina-12/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias Mamárias Experimentais/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Tomografia por Emissão de Pósitrons , Ratos
19.
Hum Gene Ther ; 20(2): 125-36, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18937552

RESUMO

A genetic vaccine platform based on DNA electroporation (DNA-EP) and adenovirus (Ad) was used to generate immune response against human carcinoembryonic antigen (CEA) and antitumor effects in murine models with spontaneous tumors arising in an orthotopic location. CEA transgenic (CEA.Tg) mice treated with the carcinogen 1,2-dimethylhydrazine developed CEA-overexpressing tumors that resembled human sporadic colorectal cancer. APC1638N/CEA hybrid mice, generated by crossing mice carrying the adenomatous polyposis coli (Apc1638N) gene mutation with CEA.Tg mice, are representative of human familial polyposis and develop polyps that overexpress the antigen. In both models, the DNA-EP/Ad vaccine succeeded in breaking immune tolerance and achieved significant antitumor effects in therapeutic settings. Our data suggest that genetic vaccines targeting CEA may be feasible strategies against gut tumors that overexpress the antigen. In addition, these models are powerful systems for evaluating antigen-specific tumor immunity and assessing therapeutic vaccine strategies for human colorectal cancer.


Assuntos
Pólipos Adenomatosos/terapia , Vacinas Anticâncer/uso terapêutico , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/terapia , Vetores Genéticos , Pólipos Adenomatosos/imunologia , Pólipos Adenomatosos/patologia , Adenoviridae/genética , Animais , Vacinas Anticâncer/genética , Antígeno Carcinoembrionário/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Vetores Genéticos/genética , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Padrões de Referência , Regulação para Cima
20.
PLoS One ; 3(1): e1508, 2008 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-18231595

RESUMO

A novel and efficient tagArray technology was developed that allows rapid identification of antibodies which bind to receptors with a specific expression profile, in the absence of biological information. This method is based on the cloning of a specific, short nucleotide sequence (tag) in the phagemid coding for each phage-displayed antibody fragment (phage-Ab) present in a library. In order to set up and validate the method we identified about 10,000 different phage-Abs binding to receptors expressed in their native form on the cell surface (10 k Membranome collection) and tagged each individual phage-Ab. The frequency of each phage-Ab in a given population can at this point be inferred by measuring the frequency of its associated tag sequence through standard DNA hybridization methods. Using tiny amounts of biological samples we identified phage-Abs binding to receptors preferentially expressed on primary tumor cells rather than on cells obtained from matched normal tissues. These antibodies inhibited cell proliferation in vitro and tumor development in vivo, thus representing therapeutic lead candidates.


Assuntos
Anticorpos Monoclonais/genética , Bacteriófagos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacocinética , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ressonância de Plasmônio de Superfície
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